Pediatric Depression from an Integrative Perspective · • Exercise – reduces cortisol levels...
Transcript of Pediatric Depression from an Integrative Perspective · • Exercise – reduces cortisol levels...
Pediatric Depression from an Integrative Perspective
scott shannon, md faacapuniversity of colorado
Agenda
� Our current situation� New ways of thinking � Depression� Treatment options� Bipolar and Ketamine
Unanticipated Consequences
New York Times Lead Story: April 7, 2018
Depression as a Model
� Environmental, physical, emotional, mental, social, or spiritual triggers
� Final common pathway
� Lack of core pathophysiology
� Very broad assessment needed
� Unique expression of imbalance
New ways of thinking
A new wilderness to navigate
Overweight Children in US CDC
0%
5%
10%
15%
20%
71-74 76-80 88-94 99-00 2001-02
2003-04
age 6-11age 12-19
IL-6 Predicts later illness� 4,500 children assessed age 9 and again at 18 years
old (ALSPAC).
� Measured IL-6. Broken into thirds
� High group 2x as likely to develop depression or schizophrenia
� Higher levels associated with risk in dose-dependent manner
Khandaker, GM JAMA Psychiatry 2014 Aug 13 epub 1332
Does inflammation change psychiatric outcomes?
� Etanercept (Enbrel) improved MDD more than placebo in psoriasis study � Tyring 2006
� Adjunctive aspirin speeds response time to SSRI (fluoxetine) for depression phenotype in rats � Mendlewicz 2006
� Adjuctive celecoxib (Celebrex) improves outcomes to SNI (reboxetine) for MDD � Muller 2006
� In animal models, cytokine antagonists and anti-inflammatory drugs block depression phenotype after immune activation. � Dantzer 2008
Contributors to inflammation
• Abnormal microbiome
• Trauma = ACEs: inflammation via SNS activation
• Stress
• Obesity or metabolic syndrome
• Diet, SAD, GMOs, HFCS, sugar
• Toxic burden, amalgam fillings, organic pollutants
• Infections
• Intestinal permeability (leaky gut)
• Injury, surgery
Decreasing Inflammation• Diet – loose weight and eat well
– Mediterranean, Anti Inflammatory Diet for Dummies, New Atkins Diet, low carb diet.
• Exercise – reduces cortisol levels • Meditation and other mind/body therapies• Supplements
– Omega 3 Fatty Acid, 2G daily– Ashwaganda, 500mg bid– N Acetyl Cysteine, 1G bid– Vitamin D, 5,000iu/day
• Medications– Statins, TCAs, Lovaza (Omega 3)
Mitochondrial Modulation� CNS function places huge demands on energy
production
� There is increasing recognition that mitochondrial dysfunction may play a critical role in major psychiatric illness
� Symptoms of mito dys: anxiety, mood d/o, cognitive dysfunction, psychosis and OCD
� Studies correlate anxiety with mitochondrial abn in hippocampus
Anglin RE Transl Psychiatry 2012 November 13
Mitochondrial Modulation Known Modulators:
� 1. N-acetyl Cysteine (NAC)
� 2. Acetyl-L-Carnitine
� 3. S-adenosyl Methionine (SAM-e)
� 4. CoQ10
� 5. Alpha-Lipoic Acid
� 6. Creatine Monohydrate
� 7. Melatonin
Nierenberg AA Aust NZ J Psychiatry 2012, June 18
Huge in US: athletes and body builders
Buff up the Brain?� Creatine monohydrate (CM) used to build muscle
mass
� Creatine Kinase (CK) plays key role in energy metabolism
� Serum CK fluctuates with mood, depression and bipolar phase
� May be gender differential-only female rats respond
� 3-5 gm q am
Allen PJ Neuroscience Biobehavioral Review 2012, 36 (5): 1442-1462.
Creatine in Teens � Pilot study with creatine for augmentation and MRI
spectroscopy comparison with controls
� 5 teen girls with TRD who failed fluoxetine
� 4 grams daily for 4 weeks
� Mean CDRS fell from 69 to 30
� A significant increase in brain Phosphocreatine (PCr) concentration (p=0.02) on follow-up
Kondo, D J Affective DO 2011 135 (0): 354
Peds: Exercise for Depression
� Meta-analysis: 50 studies (89, 894 pts). 2000-15
� Mean effect size: Significant (r = -0.14; 95% confidence interval [CI] = -0.19 to -0.10)
� Stronger effect sizes: measures of frequency and intensity of physical activity versus intensity alone
Korczak, D et al Pediatrics 2017, 139 (4).
Chronotherapeutics � RCT of 62 adolescents (13-18 yrs) with moderate
to severe depression
� Compared bright light therapy vs wake therapy
� BLT effective for mood at two weeks post intervention
� No added benefit with WT to mood
� Sleep quality improved in both groups
Gest, S et al Eur Child Adol Pyschiatry 2016 Feb;25(2):151-61
Cookbook from the1940’s
St John’s wort: Cochranel 29 studies from a variety of countries with
5,489 patients, randomized and double blind.
l Major Depression only
l Placebo or antidepressants
l Superior to placebo in treating patients with major depression and are "similarly effective" as standard antidepressants
Linde K, et al Cochrane Database of Systematic Reviews 2008, 4. October
Systemic Review of SJW vs Antidepressants
Apayden, E et al, Syst Rev 2016; 5(1): 148.
St. John’s wort: Risks Cytochrome P450 effects-Decreases potency of:l BCPl Cyclosporinel Digoxinl Warfarinl Protease inhibitorsl Theophyline
Increases potency of: MAOi, SSRI, Alcohol, triptans, narcotics
St. John’s wort l Safe, effective treatment for depression
(mild to major)
l No Black Box warning
l Use quality product; 0.3% hypericins is a general marker
l Cost $8–20 per month
l BID dosing best: 900mg/day total, age 8 up
SAM-e in Depression
About the same as SSRI
SAM-e
� S–adenosyl methionine (crucial methyl donor)� Enhances methylation in body� Safe and synergistic antidepressant� Stimulating, works quickly (2 weeks)� Headache, insomnia, nausea� 200-800 mg twice daily, start low, give on
empty stomach� Can induce mania
Saffron
Saffron (crocus sativus)� Greek frescos depict Saffron as medicine 3600
years ago
� Herbalists: antispasmodic, thymoleptic, carminative, cognition enhancer, aphrodisiac, and emmenagogue.
� Stigma and petals both studied
� 15 mg-30mg twice daily used in all studies
Saffron in Depression and Anxiety
� Systemic Review and Meta-analysis
� 23 RCTs
� Large effect sizes Depression (0.99); Anxiety (0.95)
� Augmentation helpful: (1.23)
� Concern: possible publication bias and regional concern
Marx, W Nutrition Review 2019 May 28. pii: nuz023
Depression Treatments: Mental/Emotional
� Psychotherapy-indiv and family
� Recreation
� Social/Relationships
� Work
� Hobbies
� Education
Depression Treatments: Spiritual
� Retreat and Nature
� Spiritual Counseling
� Dream Work
� Service
� Existential Exploration
� Prayer
� Love, Joy, Hope
Support Energy� Adaptogens-Rhodiola: 2-400mg/am
� Acetyl L Carnitine: 1-2,000mg/d
� CoQ 10: 100-200mg/d
� B Complex 50 mg in am
� Vit C: 500-1,000mg BID
� Think gut and candida
� Explore sleep, think apnea
� Retreat
� Calamity
� Psychedelics
� Shamanic journey
� Spiritual conversion
� World travel/pilgrimage
� Near death experiences (NDE)
� Major events: birth, illness, divorce and death
Catalysts for Profound Change
Depression: tools
� Supplements
� CES
� Exercise
� Acupuncture
� Hormones
� Light
� Medications
� Meditation
� Heavy metals removal
� Cognitive work (CBT/DBT)
� Gut/ Food Allergies
� Diet
� Family/Couples work
� New job/career
� Spiritual work
� Animals/pets
� Mitochondria
� Herbal remedies
Assessment: Lab� Thyroid: TSH, T3 and T4� Adrenal: DHEA-s & salivary cortisols� CBC/ferritin and Cholesterol� B-12 and folate� GI/dysbiosis: elimination diet� Vitamin D � Homocysteine� High Sens CRP� MTHFR
Depression-opinion what to avoid
� Over emphasizing the physical
� Over emphasizing medications
� Getting stuck in a narrow path
� Forgetting psychotherapy
� Forgetting family dysfunction
� Adding medications to medications
Depression: opinion what to do
� Evaluate all ecosystems
� Explore and support diet and sleep fully
� Exercise
� Supplements: SAM-e, SJW, Vit C, Saffron, Rhodiola, etc.
� Low energy-diet/gut, adrenals or mitochondria
� Explore sleep fully
� Rule out inflammation and toxic overload
� Address software and family issues
� Inspire the patient to make changes
Opinion: Depression� SJW or SAMe or Saffron based on patient
� B Complex 50mg (B-6 and 1 mg methylfolate)
� EPA: 1 gram or more
� Vitamin C: 500-1,000 mg
� Exercise
� Higher protein, high quality diet
� Consider mitochondrial modulation or adaptogen if energy concern
� Psychotherapy or education
� Light therapy/sunlight
Bipolar Disorder in Kids � Previously extremely rare
� Increasing rates—40 fold rise in Dx in 10 yrs
� Cultural, nutritional roots
� Omega 3 oil deficiency=inflammatory CNS?
� ADHD 80-90% co morbid
� Anxiety, hallucinations, suicidality common Moreno, C. Archives Gen Psychiatry September 64 (9) 2007
Integrative Tx of Bipolar D/O
� Broad-Spectrum Micronutrients
� Parenting and Family Therapy
� Omega-3 (one gram EPA)
� Inositol (2 to 5 grams TID)
� Bright Light Therapy (10,000 lux; 18 inches; 30min)
� Rhodiola/Ashwaganda
� Others
Ketamine and Depression
“The marked acute antidepressant efficacy of ketamine, even in medication-refractory patients, now seems beyond doubt. A meta-analysis of 9 ketamine RCTs (pooled N = 234) found that ketamine attenuated depression significantly more than did control treatment. The antidepressant benefits were apparent at 40 minutes, peaked at day 1, and were lost by days 10–12.”
Andrade, C J Clinical Psychiatry 2017 Apr;78(4):e415-e419.
Summary
� Our current system has many limitations
� We need to approach each person as a complex ecosystem
� Evidenced based treatments like SAMe, SJW, exercise and other treatments offer helpful options for depression
Nutrient deficiency can cause disease
“When one input in the metabolic network is inadequate, repercussions are felt on a large number of systems and can lead to…disease.” Ames BN. J Nutr. 2004 Nov;134(11)
What is a broad-spectrum, or multi-ingredient, micronutrient formula?
� The Original Formula Prototype: EMP, then: � EMPowerplus™ � Daily Essential Nutrients™; � Quiet Minds™
� ’36-ingredients’ (Minerals and Vitamins, plus some antioxidants, AAs and botanicals)
� Other Formulas in the Medical Literature � Berocca™, Swisse Ultivite (Men’s, Women’s) F1™,
Syndion™, Tropamine™, and other proprietary and non-proprietary products
Broad-Spectrum Micronutrients
Daily Essential Nutrients™(and EMPowerplus™,QuietMinds™)
DEN: Serving size = 4; U&C full dose = 4 TID; capsule and powder preps
� 39 ingredients: 16 minerals, 13 vitamins, and 10 in the ‘proprietary blend’ (choline, inositol, AAs, botanicals, trace minerals)
� Includes, per serving: D (1000 IU), folate (267 mcg as L-5-MTHF ), K (40 mcg as 3:1 K1:K2), and lithium ( ̴333 mcg as orotate)
� No citrus bioflavonoids, L-glutamine, DL-phenylalanine, or germanium sesquioxide; yet includes αLA, NAC, and ALC which are not in EMP.
E.M. Power Plus
� Vitamins: A, C, D, E, B1, B2, B3, B6, B9, B12 � Biotin, Pantothenic Acid, Calcium � Iron, Phosphorous, Iodine, Magnesium � Zinc, Selenium, Copper, Manganese � Phenylalanine, Glutamine, Bioflavanoids � Grape seed, Ginkgo, Inositol � Vanadium, Boron, Methionine, Germanium, Nickel � Currently over 38 peer reviewed studies published,
all done w/o $ support from manufacturer
Next Generation of EMP
� Daily Essential Nutrients
� Contains Vitamin K
� Doubles dose of Vitamin D
� No citrus bioflavinoids
� Contains acetylcarnitine and NAC
� Contains organic lithium
� Much less nausea and med interaction
Daily Essential Nutrients™ (DEN)
� This is the foundation nutraceutical biotx for the manic state
� W/O psych meds on board – rapid titration from 2→3→4 TID w/meals over 3-7 days
� W/concurrent psych Rxs – slower titration, depending upon the class(es) of Rx(s), then reduced or tapered off � Monitor for biodynamic interactions and
increased incidence of SEs � 4 TID remains the full-dose goal
dozens of publications later
� “Ingesting minerals and vitamins in combination makes physiological sense, and research on the use of broad-spectrum formulations for psychiatric symptoms is increasing rapidly.” � 43 original investigations / PRISMA systematic review
covering 5 major areas Rucklidge JJ, Kaplan BJ. Expert Rev. Neurother. (2013)
� As of March 2020, more than 38 empirical reports on EMPowerplus™ for various mental conditions published in peer-reviewed medical journals; not funded by the manufacturer or its business affiliates
� Many other publications on bsMCNs for conditions of interest to psychiatrists
Ketamine increases neuroplasticity
Huang YJ et al. Neural Plast. 2017;2017:4605971.
Dore et al, J Psychoactive Drugs 2019, 2019 Apr-Jun;51(2):189-198.
Dore et al 2019.
Troughs and Attractors
Simplified visualization of brain hub and network activity
Placebo Psilocybin
Psilocybin: Creates less rigid and more open connections
Petri G, J R Soc Interface 2014; 11(101):20140873.
Resources Culbert and Olness (ed) Integrative Pediatrics Oxford Univ Press: NY, 2010
Diller, L Running on Ritalin Bantam Books: NYC, 1998
Doidge, N The Brain That Changes Itself, Penguin: NYC, 2007
Greene, R The Explosive Child Harper Collins, NY, 2005
Honos-Webb, L The Gift of ADHD New Harbinger: Oakland, Ca, 2010
Kemper, K Mental Health Naturally AAP Press: Elk Village, Il, 2010
Newmark, S ADHD without Drugs Nurtured Heart Tucson, 2010
Shannon, S Handbook of Complementary and Alternative Therapies in Mental Health, Academic Press: San Diego, CA, 2002
Shannon, S Mental Health for the Whole Child Norton: NY, 2013
Shannon, S Parenting the Whole Child Norton: NY, 2014
ResourcesEmmons, H., The Chemistry of Joy Simon and Schuster: NYC, 2006
Kemper, K., Mental Health, Naturally AAP: Elk Grove, Il, 2010
Lake, J and Spiegel D Complementary and Alternative Treatments in Mental Health Care APPI: Washington DC, 2007.
Lake J Textbook of Integrative Mental Health Care Thieme Medical Publishers: NY, 2007
Larsen, J. Seven Weeks to Sobriety Ballentine Books: NY 1997
Logan, A., The Brain Diet Cumberland House: Nashville TN, 2007
Murray, M., Encyclopedia of Nutritional Supplements, Prima Press: NY 1996
Pizzorno, J. and Murray, M., Encyclopedia of Natural Medicine, Prima Press: NY 1997
Ratey, J., Spark: Exercise and the Brain Little, Brown: NYC, 2008
Shannon, S., Handbook of Complementary and Alternative Therapies in Mental Health, Academic Press: San Diego, CA 2002
Zuess, J., The Wisdom of Depression, Harmony Books: NY 1998
Scott Shannon, MD
Wholeness Center2620 E Prospect Rd. #190
Fort Collins, Colorado 80525970.221.1106 [email protected]
www.wholeness.com